ArticleOncogene2020
PRRG4 promotes breast cancer metastasis through the recruitment of NEDD4 and downregulation of Robo1.
Article in Oncogene, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- E3 Ubiquitin Ligases in Breast Cancer Metastasis: A Systematic Review of Pathogenic Functions and Clinical Implications.Frontiers in oncology · 2021Pooled it
- Repression of ROBO1 Enhances Cisplatin Sensitivity in Hypermethylated Subtype of HPV-Positive Head and Neck Carcinoma.Cancer science · 2026Article
- A novel therapeutic monoclonal antibody targeting PZR demonstrates potent anti-metastatic efficacy in triple-negative breast cancer.Journal of translational medicine · 2026Article
- Identification of PRRG1 as a possible molecular target of pancreatic cancer.Cell death & disease · 2026Article
- Article
- PRRG4 Brain-Specific Conditional Knockout Mice Display Autism Spectrum Disorder-Like Behaviors.Biological procedures online · 2025Article
- ROBO1 enhanced esophageal carcinoma cell radioresistance through accelerating G3BP2-mediated eIF3A degradation.Cell death & disease · 2025Article
- NEDD4 facilitates the progression of endometrial carcinoma by enhancing PAMR1 protein degradation through ubiquitination.Functional & integrative genomics · 2025Article
- NEDD4 enhances bone‑tendon healing in rotator cuff tears by reducing fatty infiltration.Molecular medicine reports · 2025Article
- Emerging roles for E3 ubiquitin ligases in neural development and disease.Frontiers in cell and developmental biology · 2025Review
- Role and therapeutic potential of the NEDD4 family in breast cancer.Frontiers in pharmacology · 2025Review
- Telomerase related molecular subtype and risk model reveal immune activity and evaluate prognosis and immunotherapy response in prostate cancer.Cancer cell international · 2024Article
- NEDD4 and NEDD4L: Ubiquitin Ligases Closely Related to Digestive Diseases.Biomolecules · 2024Review
- CircSEMA6A upregulates PRRG4 by targeting MiR-520h and recruiting ELAVL1 to affect cell invasion and migration in papillary thyroid carcinoma.Archives of endocrinology and metabolism · 2024Article
- Oncoprotein SET-associated transcription factor ZBTB11 triggers lung cancer metastasis.Nature communications · 2024Article
- Ubiquitin ligase NEDD4 promotes the proliferation of hepatocellular carcinoma cells through targeting PCDH17 protein for ubiquitination and degradation.The Journal of biological chemistry · 2024Article
- PRRG4 regulates mitochondrial function and promotes migratory behaviors of breast cancer cells through the Src-STAT3-POLG axis.Cancer cell international · 2023Article
- Gene Signature Associated with Nervous System in an Experimental Radiation- and Estrogen-Induced Breast Cancer Model.Biomedicines · 2023Article
- Article
- Circ_0056618 enhances PRRG4 expression by competitively binding to miR-411-5p to promote the malignant progression of colorectal cancer.Molecular and cellular biochemistry · 2023Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metastasis is responsible for the death of most breast cancer patients. Robo1 has been implicated as a tumor suppressor for various cancers including breast cancer. However, it is not well understood how Robo1 expression is regulated during tumorigenesis. In this study, we uncovered that the transmembrane proline rich γ-carboxyglutamic acid protein 4 (PRRG4) promotes breast cancer metastasis by downregulating Robo1. Analysis of mRNA expression data in The Cancer Genome Atlas and immunohistochemistry assay on breast tumor samples showed that PRRG4 expression was higher in breast tumors than in normal breast tissues. Experiments with PRRG4 knockdown and overexpression revealed that PRRG4 promoted migration and invasion of breast cancer cells, and enhanced metastasis in an experimental metastasis model. Mechanistically, we found that PRRG4 via its LPSY and PPPY motifs recruited the E3 ubiquitin ligase NEDD4, which induced ubiquitination and degradation of Robo1, thus contributing to migration and invasion of breast cancer cells. In addition, PRRG4 interacted with and enhanced protein tyrosine kinase Src and FAK activation. Overall, our data support a model that PRRG4 via NEDD4 downregulates the Robo1, resulting in the activation of Src and FAK and promoting breast cancer metastasis. PRRG4 may be a novel target for treating metastatic breast cancer.
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